【摘要】 用量子化学密度泛函理论（DFT）、分子力学（MM+）及回归分析方法，对一系列抗癌性吲哚喹唑啉衍生物进行了定量构效关系（QSAR）的研究．通过回归分析，筛选了影响抗癌活性的主要因素，建立了定量构效关系方程．结果表明，化合物的最低未占据分子轨道（LUMO）与最高占据分子轨道（HOMO）之间的能量差(Δ_εL-H)、分子的疏水性（IgP）以及环 D 上的总电荷（∑Q_D）和环 D 上 R₁ 取代基的第一个原子的净电荷(Q_FR1)是影响化合物抗癌活性的主要因素．所得模型对化合物抗癌活性有较好的预测效果．同时，与Δε_L-H密切相关的 LUMO 轨道能量及共轭平面面积对药物的 DNA-结合及其活性起着十分重要的作用，可通过选取具有较强的拉电子性质同时又能与本系列化合物的骨架形成更大共轭体系的取代基 R₁,设计抗癌活性较高的化合物．更多还原

【Abstract】 The quantitative structure-activity relationship（QSAR）of indolo[1,2-b]quinazoline derivatives,inregard to their antitumor activity,was systematically studied using the density functional theory（DFT）,molec-ular mechanism（MM+）and regression analysis methods.Via a stepwise regression analysis,some main in-dependent factors affecting the activity of the compounds were selected out,and then the QSAR equation wasestablished.It has been found that the energy difference(△ε_L-Hbetween the lowest unoccupied molecular orbital（LUMO）and the highest occupied molecular orbital（HOMO）of the compound,the hydrophobic parameter（lg P）of the molecule,as well as the total net charge（ΣQ_D）of the D-ring skeleton and the net charge(Q_FR1ofthe first atom of the substituent R₁ on D-ring are the main independent factors contributing to the antitumor ac-tivity of the compound.The cross-validation r_cv² and the fitting correlation coefficient r² for the model estab-lished by this study are 0.7364 and 0.8505,respectively.The results suggest that this model has good pre-dictability and further indicate that the LUMO energy closely relative to △ε_LHand the conjugative planarity areaplay a very important role in the DNA-binding and the activity of the compounds.Therefore,some higher an-titumor active compounds can be designed prior to their synthesis via selecting some substituents（R₁）which havestronger electron-withdrawing ability and can form greater conjugative planarity area with the skeletons of theseries of the compounds.更多还原